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Strong, ongoing high-latitude warming is causing changes to vegetation composition and plant productivity, modifying plant emissions of biogenic volatile organic compounds (BVOCs). In the sparsely populated high latitudes with clean background air, climate feedback resulting from BVOCs as precursors of atmospheric aerosols could be more important than elsewhere on the globe. Here, we quantitatively assess changes in vegetation composition, BVOC emissions, and secondary organic aerosol (SOA) formation under different climate scenarios. We show that warming-induced vegetation changes largely determine the spatial patterns of future BVOC impacts on SOA. The northward advances of boreal needle-leaved woody species result in increased SOA optical depth by up to 41%, causing cooling feedback. However, areas with temperate broad-leaved trees replacing boreal needle-leaved trees likely experience a large decline in monoterpene emissions and SOA formation, causing warming feedback. We highlight the necessity of considering warming-induced vegetation shifts when assessing land radiative feedback on climate following the BVOC-SOA pathway. [ABSTRACT FROM AUTHOR]

Defoliation caused by strong tropical cyclones can modify the partitioning of incident solar radiation between the sensible, latent, and substrate heat fluxes. While previous work has shown hurricane defoliation to warm near-surface air temperature along its track, this study more directly contextualizes the warming to human heat stress and exposure via the heat index (HI). For this case study, the spatial extent and temporal persistence of defoliation produced by Hurricane Laura (2020) in southwestern Louisiana was characterized using the normalized difference vegetation index (NDVI). The defoliated land surface was then assimilated into the Weather Research and Forecasting (WRF) model version 4.2 and compared to a control, normal-foliage simulation for the 30 days following landfall. Over southwest Louisiana, the largest HI increase occurred at 0600 UTC (1:00 AM LT) with an average increase of + 0.25 °C, and the exposure time to HI ≥ 30 °C increased by 8.1% after accounting for the defoliated landscape. Meanwhile, Cameron, Louisiana, the site of Laura's landfall where defoliation was most severe, cumulatively experienced an extra 33 h of HI values exceeding 26 °C, while mean HI increased by 1.2 °C at 0300 UTC. Additional WRF experiments were performed with altered "landfall" years of 2017 and 2018 to determine the sensitivity of defoliation-driven HI changes to the ambient synoptic conditions. While synoptic conditions modulated the magnitude of increase, HIs nonetheless experienced statistically significant increases in both hypothetical "landfall" years. Such findings are valuable for emergency managers and community health officials because overnight minimum temperatures are a strong indicator of heat mortality. [ABSTRACT FROM AUTHOR]

Human visual systems have evolved to extract ecologically relevant information from complex scenery. In some cases, the face in the crowd visual search task demonstrates an anger superiority effect, where anger is allocated preferential attention. Across three studies (N = 419), we tested whether facial hair guides attention in visual search and influences the speed of detecting angry and happy facial expressions in large arrays of faces. In Study 1, participants were faster to search through clean-shaven crowds and detect bearded targets than to search through bearded crowds and detect clean-shaven targets. In Study 2, targets were angry and happy faces presented in neutral backgrounds. Facial hair of the target faces was also manipulated. An anger superiority effect emerged that was augmented by the presence of facial hair, which was due to the slower detection of happiness on bearded faces. In Study 3, targets were happy and angry faces presented in either bearded or clean-shaven backgrounds. Facial hair of the background faces was also systematically manipulated. A significant anger superiority effect was revealed, although this was not moderated by the target's facial hair. Rather, the anger superiority effect was larger in clean-shaven than bearded face backgrounds. Together, results suggest that facial hair does influence detection of emotional expressions in visual search, however, rather than facilitating an anger superiority effect as a potential threat detection system, facial hair may reduce detection of happy faces within the face in the crowd paradigm. [ABSTRACT FROM AUTHOR]

Type A GABA (γ-aminobutyric acid) receptors represent a diverse population in the mammalian brain, forming pentamers from combinations of α-, β-, γ-, δ-, ε-, ρ-, θ- and π-subunits1. αβ, α4βδ, α6βδ and α5βγ receptors favour extrasynaptic localization, and mediate an essential persistent (tonic) inhibitory conductance in many regions of the mammalian brain1,2. Mutations of these receptors in humans are linked to epilepsy and insomnia3,4. Altered extrasynaptic receptor function is implicated in insomnia, stroke and Angelman and Fragile X syndromes1,5, and drugs targeting these receptors are used to treat postpartum depression6. Tonic GABAergic responses are moderated to avoid excessive suppression of neuronal communication, and can exhibit high sensitivity to Zn2+ blockade, in contrast to synapse-preferring α1βγ, α2βγ and α3βγ receptor responses5,7–12. Here, to resolve these distinctive features, we determined structures of the predominantly extrasynaptic αβ GABAA receptor class. An inhibited state bound by both the lethal paralysing agent α-cobratoxin13 and Zn2+ was used in comparisons with GABA–Zn2+ and GABA-bound structures. Zn2+ nullifies the GABA response by non-competitively plugging the extracellular end of the pore to block chloride conductance. In the absence of Zn2+, the GABA signalling response initially follows the canonical route until it reaches the pore. In contrast to synaptic GABAA receptors, expansion of the midway pore activation gate is limited and it remains closed, reflecting the intrinsic low efficacy that characterizes the extrasynaptic receptor. Overall, this study explains distinct traits adopted by αβ receptors that adapt them to a role in tonic signalling.Cryo-electron microscopy structures are used to identify mechanisms underlying distinct features of extrasynaptic type A γ-aminobutyric acid receptors. [ABSTRACT FROM AUTHOR]

Late sodium current (late INa) inhibition has been proposed to suppress the incidence of arrhythmias generated by pathological states or induced by drugs. However, the role of late INa in the human heart is still poorly understood. We therefore investigated the role of this conductance in arrhythmias using adult primary cardiomyocytes and tissues from donor hearts. Potentiation of late INa with ATX-II (anemonia sulcata toxin II) and E-4031 (selective blocker of the hERG channel) slowed the kinetics of action potential repolarization, impaired Ca2+ homeostasis, increased contractility, and increased the manifestation of arrhythmia markers. These effects could be reversed by late INa inhibitors, ranolazine and GS-967. We also report that atrial tissues from donor hearts affected by atrial fibrillation exhibit arrhythmia markers in the absence of drug treatment and inhibition of late INa with GS-967 leads to a significant reduction in arrhythmic behaviour. These findings reveal a critical role for the late INa in cardiac arrhythmias and suggest that inhibition of this conductance could provide an effective therapeutic strategy. Finally, this study highlights the utility of human ex-vivo heart models for advancing cardiac translational sciences. [ABSTRACT FROM AUTHOR]

Synthetic biology is a powerful tool to create therapeutics which can be rationally designed to enable unique and combinatorial functionalities. Here we utilize non-pathogenic E coli Nissle as a versatile platform for the development of a living biotherapeutic for the treatment of cancer. The engineered bacterial strain, referred to as SYNB1891, targets STING-activation to phagocytic antigen-presenting cells (APCs) in the tumor and activates complementary innate immune pathways. SYNB1891 treatment results in efficacious antitumor immunity with the formation of immunological memory in murine tumor models and robust activation of human APCs. SYNB1891 is designed to meet manufacturability and regulatory requirements with built in biocontainment features which do not compromise its efficacy. This work provides a roadmap for the development of future therapeutics and demonstrates the transformative potential of synthetic biology for the treatment of human disease when drug development criteria are incorporated into the design process for a living medicine. Synthetic biology can be used to create rationally designed living therapeutics. Here the authors engineer E. coli Nissle to target STING activation in antigen presenting cells for the treatment of solid tumors and demonstrate preclinical activity in murine models. [ABSTRACT FROM AUTHOR]

Effects of non-cardiac drugs on cardiac contractility can lead to serious adverse events. Furthermore, programs aimed at treating heart failure have had limited success and this therapeutic area remains a major unmet medical need. The challenges in assessing drug effect on cardiac contractility point to the fundamental translational value of the current preclinical models. Therefore, we sought to develop an adult human primary cardiomyocyte contractility model that has the potential to provide a predictive preclinical approach for simultaneously predicting drug-induced inotropic effect (sarcomere shortening) and generating multi-parameter data to profile different mechanisms of action based on cluster analysis of a set of 12 contractility parameters. We report that 17 positive and 9 negative inotropes covering diverse mechanisms of action exerted concentration-dependent increases and decreases in sarcomere shortening, respectively. Interestingly, the multiparametric readout allowed for the differentiation of inotropes operating via distinct mechanisms. Hierarchical clustering of contractility transient parameters, coupled with principal component analysis, enabled the classification of subsets of both positive as well as negative inotropes, in a mechanism-related mode. Thus, human cardiomyocyte contractility model could accurately facilitate informed mechanistic-based decision making, risk management and discovery of molecules with the most desirable pharmacological profile for the correction of heart failure. [ABSTRACT FROM AUTHOR]

Psychological trauma is a silent epidemic which presents as a global public health issue, often in the form of post-traumatic stress disorder (PTSD). Eye Movement Desensitisation and Reprocessing (EMDR) Therapy is an empirically supported treatment intervention for PTSD and has been used as part of trauma-capacity building, particularly in low- and middle-income countries (LMIC). For some survivor's, their trauma experiences cannot be spoken of: they may be alluded to, suggested and though not directly expressed. There are several factors as to why these implicit trauma experiences are 'unspoken', for example, when the trauma involves a deep-rooted sense of shame or guilt, a distorted sense of over-responsibility or when to speak of the trauma engenders fear of retribution, reprisal and consequence. This paper will explore the effectiveness of using two protocol variations of EMDR Therapy—standard versus a 'Blind 2 Therapist' protocol version as part of a quasi-experimental study which took place in Northern Iraq. The study contains two projects and subsequently tested several hypotheses regarding safety, effectiveness, efficiency and relevance of the 'Blind 2 Therapist' protocol within EMDR Therapy. Results indicated support for the B2T protocol intervention with various trauma populations including Yezidi survivors of Islamic State of Iraq and the Levant (ISIL)—also known as Daesh. [ABSTRACT FROM AUTHOR]

The 2017 and 2018 Atlantic hurricane seasons poignantly illustrated the dangers tropical cyclones pose to US, Central American, and Caribbean coastlines. In particular, Hurricane Maria inflicted widespread damage, including catastrophic defoliation, to Puerto Rico, altering surface heat fluxes and possibly modifying precipitation patterns. This study assesses whether defoliation-driven changes to surface energy fluxes redistribute precipitation in the months following a powerful hurricane landfall. Remote sensing analyses of Maria-related vegetation reduction and recovery from Puerto Rico were adapted to the Georgia coastline. In this novel methodology, the resulting landscape evolution, characterized by an instantaneous vegetation reduction with a gradual recovery, was assimilated into the Weather Research and Forecasting model at a convection-allowing a 3-km grid spacing for the 1 June–1 August 2017 period. The experiment revealed that Maria-scale defoliation reduced precipitation by 14% during the month following landfall within a 50 × 50 km zone containing the hypothetical landfall location. A maximum deficit of 20.0% was reached 4 weeks after landfall. For June 2017, the modeled 14% deficit would have shifted the precipitation total from the 61st to the 47th percentile for years 1981–2016. Meanwhile, precipitation totals were unchanged on the domain scale. The near-landfall drying was also evident in three less-severe defoliation simulations, suggesting that systematic precipitation redistribution near the landfall location is possible following storms considerably weaker than Hurricane Maria. Analyses of the temperature and wind fields suggest that coastal kinematic flow is altered by the introduction of a thermally driven pressure gradient in the defoliated zone. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of medical or surgical treatment prior to embryo transfer in women with elevated endometrial BCL6 expression and suspected endometriosis in a prospective, cohort study design at a university-associated infertility clinic. Methods: All subjects had at least 1 year of unexplained infertility (UI) and each prospectively underwent endometrial biopsy and immunostaining for the oncogene BCL6, prior to embryo transfer during an assisted reproductive technology (ART) cycle. To be included, subjects had to have an abnormal BCL6 result, defined by elevated HSCORE ≥ 1.4. Women that were pre-treated with laparoscopy or medical suppression with GnRH agonist (depot leuprolide acetate; Lupron®, Abbvie, Inc., Chicago, IL) for 2 months were compared to a group that went untreated (controls). Endpoints included implantation rate (IR), clinical pregnancy rate (CPR), and live birth rate (LBR), and as well as cycle characteristics. Miscarriage rate were also compared between treatment and control group. Results: Women in each group had similar characteristics. Those treated by medical suppression and those undergoing laparoscopy for endometriosis had a significantly higher LBR, (5/10; 50%; 95%CI 23.7 to 76.3%) and (11/21; 52.4%; 95%CI 32.4 to 71.7), respectively, compared to controls (4/54; 7.4%; 95%CI 2.9 to 17.6). An absolute benefit of 44.2% (16/31; 95%CI 24.6 to 61.2) and a number need to treat of 3 for those that received treatment (medical suppression and laparoscopy), compared to no treatment. Miscarriages were significantly more common in the control group. Conclusions: Women with suspected endometriosis and aberrant endometrial BCL6 expression have worse reproductive outcomes following embryo transfer, including a high miscarriage rate, poor IR, and low LBR and CPR compared to cycles pre-treated with medical and surgical management. [ABSTRACT FROM AUTHOR]

Synthetic probiotic for a human metabolic disease is taken through a drug development pathway to enable translation into clinic trials.Phenylketonuria (PKU) is a genetic disease that is characterized by an inability to metabolize phenylalanine (Phe), which can result in neurotoxicity. To provide a potential alternative to a protein-restricted diet, we engineered Escherichia coli Nissle to express genes encoding Phe-metabolizing enzymes in response to anoxic conditions in the mammalian gut. Administration of our synthetic strain, SYNB1618, to the Pahenu2/enu2 PKU mouse model reduced blood Phe concentration by 38% compared with the control, independent of dietary protein intake. In healthy Cynomolgus monkeys, we found that SYNB1618 inhibited increases in serum Phe after an oral Phe dietary challenge. In mice and primates, Phe was converted to trans-cinnamate by SYNB1618, quantitatively metabolized by the host to hippurate and excreted in the urine, acting as a predictive biomarker for strain activity. SYNB1618 was detectable in murine or primate feces after a single oral dose, permitting the evaluation of pharmacodynamic properties. Our results define a strategy for translation of live bacterial therapeutics to treat metabolic disorders. [ABSTRACT FROM AUTHOR]

Peatlands are important carbon reserves in terrestrial ecosystems. The microtopography of a peatland area has a strong influence on its carbon balance, determining carbon fluxes at a range of spatial scales. These patterned surfaces are very sensitive to changing climatic conditions. There are open research questions concerning the stability, behaviour and transformation of these microstructures, and the implications of these changes for the long-term accumulation of organic matter in peatlands. A simple two-dimensional peat microtopographical model was developed, which accounts for the effects of microtopographical variations and a dynamic water table on competitive interactions between peat-forming plants. In a case study of a subarctic mire in northern Sweden, we examined the consequences of such interactions on peat accumulation patterns and the transformation of microtopographical structure. The simulations demonstrate plausible interactions between peatland growth, water table position and microtopography, consistent with many observational studies, including an observed peat age profile from the study area. Our model also suggests that peatlands could exhibit alternative compositional and structural dynamics depending on the initial topographical and climatic conditions, and plant characteristics. Our model approach represents a step towards improved representation of peatland vegetation dynamics and net carbon balance in Earth system models, allowing their potentially important implications for regional and global carbon balances and biogeochemical and biophysical feedbacks to the atmosphere to be explored and quantified. [ABSTRACT FROM AUTHOR]

Introduction: Despite the availability of multiple effective therapies, discontinuation/switching of treatment is common for many patients with rheumatoid arthritis (RA). This study was designed to examine initiation of biologic disease-modifying anti-rheumatic drugs (bDMARDs) within the Consortium of Rheumatology Researchers of North America (Corrona) RA Registry, and characterize reasons for discontinuation. Methods: Inclusion criteria were: Corrona-registered adults (≥18 years) with RA (2002-2011); age of RA onset: ≥16 years; ≥6 months' follow-up after initiation of first/subsequent bDMARD. Patients receiving both tumor necrosis factor antagonists and non-TNF antagonists were included. Treatment discontinuation was defined as first report of stopping initial therapy or initiation of new bDMARD at/between visits, using a follow-up physician questionnaire. Results: Overall, 6209 patients met inclusion criteria and 80.7% received TNF antagonists. Median time to discontinuation/change of therapy was 25.1 months (26.5 months with TNF antagonists vs. 20.5 months with non-TNF antagonists; log-rank p < 0.0001); 82.2, 67.3, and 51.1% of patients remained on therapy at 6, 12, and 24 months, respectively. Reasons for discontinuation were captured for 49.2% of patients, including: loss of efficacy (35.8%); physician preference (27.8%); safety (20.1%); patient preference (17.9%); and no access to treatment (9.0%). Baseline factors with greatest correlation to discontinuation were modified Health Assessment Questionnaire scores, patient-reported anxiety/depression, initiation of bDMARD treatment in 2007-2010 versus 2002-2003, and Clinical Disease Activity Index scores. Conclusions: Almost one-third of patients in the US discontinue currently available bDMARD therapies for RA by 12 months and almost half by 24 months, most commonly due to loss of efficacy. Funding: Corrona LLC and MedImmune. [ABSTRACT FROM AUTHOR]

Homeostatic processes that provide negative feedback to regulate neuronal firing rates are essential for normal brain function. Indeed, multiple parameters of individual neurons, including the scale of afferent synapse strengths and the densities of specific ion channels, have been observed to change on homeostatic time scales to oppose the effects of chronic changes in synaptic input. This raises the question of whether these processes are controlled by a single slow feedback variable or multiple slow variables. A single homeostatic process providing negative feedback to a neuron's firing rate naturally maintains a stable homeostatic equilibrium with a characteristic mean firing rate; but the conditions under which multiple slow feedbacks produce a stable homeostatic equilibrium have not yet been explored. Here we study a highly general model of homeostatic firing rate control in which two slow variables provide negative feedback to drive a firing rate toward two different target rates. Using dynamical systems techniques, we show that such a control system can be used to stably maintain a neuron's characteristic firing rate mean and variance in the face of perturbations, and we derive conditions under which this happens. We also derive expressions that clarify the relationship between the homeostatic firing rate targets and the resulting stable firing rate mean and variance. We provide specific examples of neuronal systems that can be effectively regulated by dual homeostasis. One of these examples is a recurrent excitatory network, which a dual feedback system can robustly tune to serve as an integrator. [ABSTRACT FROM AUTHOR]

Type-A γ-aminobutyric acid receptors (GABAARs) are the principal mediators of rapid inhibitory synaptic transmission in the human brain. A decline in GABAAR signalling triggers hyperactive neurological disorders such as insomnia, anxiety and epilepsy. Here we present the first three-dimensional structure of a GABAAR, the human β3 homopentamer, at 3 Å resolution. This structure reveals architectural elements unique to eukaryotic Cys-loop receptors, explains the mechanistic consequences of multiple human disease mutations and shows an unexpected structural role for a conserved N-linked glycan. The receptor was crystallized bound to a previously unknown agonist, benzamidine, opening a new avenue for the rational design of GABAAR modulators. The channel region forms a closed gate at the base of the pore, representative of a desensitized state. These results offer new insights into the signalling mechanisms of pentameric ligand-gated ion channels and enhance current understanding of GABAergic neurotransmission. [ABSTRACT FROM AUTHOR]

Many graph datasets are labelled with discrete and numeric attributes. Most frequent substructure discovery algorithms ignore numeric attributes; in this paper we show how they can be used to improve search performance and discrimination. Our thesis is that the most descriptive substructures are those which are normative both in terms of their structure and in terms of their numeric values. We explore the relationship between graph structure and the distribution of attribute values and propose an outlier-detection step, which is used as a constraint during substructure discovery. By pruning anomalous vertices and edges, more weight is given to the most descriptive substructures. Our method is applicable to multi-dimensional numeric attributes; we outline how it can be extended for high-dimensional data. We support our findings with experiments on transaction graphs and single large graphs from the domains of physical building security and digital forensics, measuring the effect on runtime, memory requirements and coverage of discovered patterns, relative to the unconstrained approach. [ABSTRACT FROM AUTHOR]

The Arctic land area has warmed by >1 °C in the last 30 years and there is evidence that this has led to increased productivity and stature of tundra vegetation and reduced albedo, effecting a positive (amplifying) feedback to climate warming. We applied an individual-based dynamic vegetation model over the Arctic forced by observed climate and atmospheric CO for 1980-2006. Averaged over the study area, the model simulated increases in primary production and leaf area index, and an increasing representation of shrubs and trees in vegetation. The main underlying mechanism was a warming-driven increase in growing season length, enhancing the production of shrubs and trees to the detriment of shaded ground-level vegetation. The simulated vegetation changes were estimated to correspond to a 1.75 % decline in snow-season albedo. Implications for modelling future climate impacts on Arctic ecosystems and for the incorporation of biogeophysical feedback mechanisms in Arctic system models are discussed. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the effect of increases in exercise intensity on the sweat lactate concentration and lactate excretion rate. Eight healthy male volunteers complete a 90-min exercise bout of treadmill walking in a 35°C and 40% relative humidity environmental chamber. During the exercise trial, the subjects performed three 30-min ordered exercise bouts at 60, 70, and 80% of their age-predicted maximum heart rate (HRmax), with 10 min of rest outside the chamber between bouts. Sweat rate was measured volumetrically during each of the three exercise bouts on the flexor surface of the proximal half of the right forearm. Sweat lactate concentration ([lactate]sweat) was measured in each sample and multiplied by the forearm sweat rate to calculate the lactate excretion rate (LER). There was a significant ( P < 0.05) decrease in the [lactate]sweat at the 70 and 80% HRmax exercise intensities compared to the 60% HRmax exercise intensity. Conversely, the LER increased significantly at the highest two exercise intensities compared to the 60% HRmax exercise intensity. Such data suggest that increases in exercise intensity require an increase in lactate production, as measured by the LER. Furthermore, the decreased [lactate]sweat at the higher exercise intensities is most likely the result of increased sweat production causing a dilution effect on the [lactate]sweat, thus limiting its ability to accurately indicate the metabolic activity of the sweat gland. [ABSTRACT FROM AUTHOR]

This paper is concerned with the English-language requirements of occupations in the USA, as measured by the O*NET database. These scores are linked to employed native and foreign-born men in the 2000 Census. Earnings increase with the respondent’s proficiency in English, with the English proficiency required for the occupation, and when those with high levels of proficiency work in jobs requiring English-language skills (interaction effect). There is a strong economic incentive for the matching of worker’s English skills and the occupation’s requirements, and this matching tends to occur in the labor market. [ABSTRACT FROM AUTHOR]

The aim of the study was to elucidate the nature and efficiency of the strategies that readers with phonological dyslexia use for temporary retention of written words in Working Memory (WM). Data was gathered through a paradigm whereby participants had to identify serially presented written (target) words from within larger word pools according to their presentation order, with word pools containing code-specific distracter (CSD) words and non-code-specific distracter (NCSD) words. Analyses focused on three aspects of performance: (1) false recognition of target words; (2) correct recognition of target words; and (3) retention of word presentation order. Participants were readers with diagnosed phonological dyslexia ( n = 20, mean grade level = 9.05 [0.89]) and a control group of regular readers ( n = 25, mean grade level = 9.00 [0.76]). Results provide direct evidence that the dyslexic readers and the regular readers used essentially different memory coding strategies for the temporary retention of written words, with the former predominantly relying on a visual strategy and the latter on a phonological strategy. Findings further pinpointed a notably impoverished ability of the dyslexic readers to retain word presentation order. The implication of these findings is discussed in relation to theories predicting the acquisition and mastery of reading. [ABSTRACT FROM AUTHOR]

Analyses of data from the 2000 US Census show that the gender pay gap differs by sector of employment and according to the part of the earnings distribution that is considered. The gender pay differential in the private sector in the US does not display either the glass ceiling or sticky floor effects that have been reported for many other countries. The government sector is, however, characterized by a distinct sticky floor effect in the female–male pay differential. Regardless of the sector of employment, females have lower hourly rates of pay than men across the entire earnings distribution. [ABSTRACT FROM AUTHOR]

Cys-loop ligand-gated ion channels mediate rapid neurotransmission throughout the central nervous system. They possess agonist recognition sites and allosteric sites where modulators regulate ion channel function. Using strychnine-sensitive glycine receptors, we identified a scaffold of hydrophobic residues enabling allosteric communication between glycine-agonist binding loops A and D, and the Zn2+-inhibition site. Mutating these hydrophobic residues disrupted Zn2+ inhibition, generating novel Zn2+-activated receptors and spontaneous channel activity. Homology modeling and electrophysiology revealed that these phenomena are caused by disruption to three residues on the '−' loop face of the Zn2+-inhibition site, and to D84 and D86, on a neighboring β3 strand, forming a Zn2+-activation site. We provide a new view for the activation of a Cys-loop receptor where, following agonist binding, the hydrophobic core and interfacial loops reorganize in a concerted fashion to induce downstream gating. [ABSTRACT FROM AUTHOR]

Zinc oxide (ZnO) thin films were deposited on various substrates by DC sputtering deposition. Thermal annealing was performed at up to 1,200°C in N2 for 30 min. The effect was investigated using x-ray diffraction (XRD), photoluminescence (PL) spectra, scanning electron microscopy (SEM), and piezoresponse force microscopy (PFM). The influence on PL response depends both on substrate material and annealing temperature. The PFM images reveal that the ZnO films have inversion domains. While annealing improves the piezoresponse, the inversion domains still persist. The cross-sectional analysis of the inversion domains shows domain boundary widths of approximately 1.5 nm. [ABSTRACT FROM AUTHOR]

Studies of immigrants' destination language acquisition to date have focused on the individual. In contrast, this paper is concerned with the relationships among family members in the determinants of destination language proficiency among immigrants. A model of immigrant language proficiency is augmented to include dynamics among family members. It is tested using data on a sample of recent immigrants. Children are shown to have a negative effect on their mother's language proficiency, but no effect on their father's. There is a substantial positive correlation between the language skills of spouses. This is due to the correlation between spouses in both the measured and the unmeasured determinants of destination language skills, even when country of origin fixed effects are held constant. [ABSTRACT FROM AUTHOR]

Analyzes a systematic approach to the ethics of research risks to address concerns regarding the ethics of research involving placebo controls, developing countries, incapable adults and emergency rooms. Key issues of interest; Analysis of pertinent topics and relevant issues; Implications on nature medicine.

Presents a study of the determinants of earnings among adult foreign-born men using the 1990 Census of Population. Discussion of modeling earnings in the immigrant labor market; Overview of selected statistics from analyses of earnings for the major birthplace regions; Impact of the minority language concentration variable on earnings within country of birth categories.

We develop a model using human capital theory and an immigrant adjustment process to generate hypotheses on the acquisition of destination-language skills among immigrants. The model is tested for adult male immigrants in the 1991 Census of Canada. Use of English or French is greater, the younger the age at migration, the longer the duration of residence, the higher the educational attainment, the farther the country of origin from Canada, and the linguistically closer the mother tongue to English or French, and among those who are not refugees, those from a former British, French, or American colony, and those who live in an area where fewer people speak the respondent's mother tongue. The explanatory variables based on birthplace have behavioral interpretations and possess almost as much explanatory power as the birthplace dummy variables. [ABSTRACT FROM AUTHOR]

In an attempt to understand the signaling pathway mediating redox-induced apoptosis, we cloned SAG, an evolutionarily conserved zinc RING finger gene that, when overexpressed, protects cells from apoptosis induced by redox agents. Here we report functional characterization of SAG by the use of yeast genetics approach. Targeted disruption of ySAG, yeast homolog of human SAG, and subsequent tetrad analysis revealed that ySAG is required for yeast viability. Complementation experiment showed that the lethal phenotype induced by the ySAG deletion is fully rescued by wildtype SAG, but not by several hSAG mutants. Complementation experiment has also confirmed that ySAG is essential for normal vegetative growth, rather than being required for sporulation. Furthermore, cell death induced by SAG deletion was accompanied by cell enlargement and abnormal cell cycle profiling with an increased DNA content. Importantly, SAG was found to be the second family member of Rbx (RING box protein) or ROC (Regulator of cullins) or Hrt that is a component of SCF E3 ubiquitin ligase. Indeed, like ROC1/Rbx1/Hrt1, SAG binds to Cul1 and SAG-Cul1 complex has ubiquitin ligase activity to promote poly-ubiquitination of E2/Cdc34. This ligase activity is required for complementation of death phenotype induced by ySAG disruption. Finally, chip profiling of the entire yeast genome revealed induction of several G1/S as well as G2/M checkpoint control genes upon SAG withdrawal. Thus, SAG appears to control cell cycle progression in yeast by promoting ubiquitination and degradation of cell cycle regulatory proteins. Oncogene (2000) 19, 2855–2866 [ABSTRACT FROM AUTHOR]

This paper uses the data on males and females from the 1989 Legalized Population Survey (LPS), a sample of aliens granted amnesty under 1986 Immigration Reform and Control Act, to analyse English language proficiency and earnings. We use a model of English language proficiency that is based on economic incentives, exposure and efficiency variables that measure the costs and benefits of aquiring English language skills. Consistent with the model, in this sample of former illegal aliens, English language proficiency is greater for those with more schooling, who immigrated at a younger age, who have been in the United States longer, with a more continuous stay, and who have less access to other origin language speakers where they live. Earnings are higher by about 8% for men and 17% for women who are proficient in both speaking and reading English, compared to those lacking both skills. [ABSTRACT FROM AUTHOR]

This paper argues that French poststructuralist theory does not represent a movement antithetical to Classics and the Classical Tradition, but should be read as its extension. Major recurring themes of poststructuralist thought are articulated at the beginning of the 1960's in Lacan's commentaries on Sophocles' Antigone and Plato's Symposium. Derrida's reading of the Phaedrus as well as his citation of the Platonic tradition in his dispute with Foucault over the latter's Histoire de la folie further confirm the importance of the Hellenic tradition to poststructuralism's engagement with occidental philosophy. Finally, Foucault's late turn to Stoicism and the philosophers of the Roman imperial period can be seen as a response to and criticism of the positions established by Lacan and Derrida. The Classics are not only relevant to understanding poststructuralist theory and philosophy, but actually define the terms of its debates. [ABSTRACT FROM AUTHOR]

Recent research on the linguistic adjustment of minority-language speaking immigrants in several destinations has found that acquisition of destination language skills is inhibited by living in an area where many others speak the same minority language. This paper uses a unique data set for Australia (1988) that includes a variety of ethnic network variables to analyze the role of the language concentration measure. These ethnic variables, in particular, ethnic press, relatives in Australia, and spouse's origin language, are highly statistically significant. Their inclusion in the equation eliminates the effect of the minority-language concentration variable. The model for analyzing the determinants of English reading and English writing skills in Australia is also shown to be very similar to the model for speaking fluency, including the effect of the ethnic network variables. [ABSTRACT FROM AUTHOR]

This paper analyzes the choice of dominant destination language spoken by immigrants in a multi-lingual destination. The empirical analysis is performed for Canada. Immigrants tend to gravitate to the official language that is closer to their mother tongue, that predominates in their region of residence and that has the broader labor market or economy. Bilingualism in the two official languages increases with the level of education in both Quebec and English Canada. French-only speakers among immigrants in Quebec tend to come from Romance language countries, have low levels of schooling, are recent arrivals and immigrated at an older age. [ABSTRACT FROM AUTHOR]

Michael Scriven has suggested that student rating forms, for the purpose of evaluating college teaching, be designed for multiple audiences (instructor, administrator, student), and with a single global item for summative functions (determination of merit, retention, or promotion). This study reviewed approaches to rating form construction, e.g., factor analytic strategies of Marsh, and recommended the multiple audience design of Scriven. An empirical test of the representativeness of the single global item was reported from an analysis of 1,378 forms collected in a university department of education. The global item correlated most satisfactorily with other items, a computed total of items, items that represented underlying factors, and various triplets of items selected to represent all possible combinations of items. It was concluded that a multiple audience rating form showed distinct advantages in design and that the single global item most fairly and highly represented the overall teaching performance, as judged by students, for decisions about retention, promotion, and merit made by administrators. [ABSTRACT FROM AUTHOR]

Neural populations with strong excitatory recurrent connections can support bistable states in their mean firing rates. Multiple fixed points in a network of such bistable units can be used to model memory retrieval and pattern separation. The stability of fixed points may change on a slower timescale than that of the dynamics due to short-term synaptic depression, leading to transitions between quasi-stable point attractor states in a sequence that depends on the history of stimuli. To better understand these behaviors, we study a minimal model, which characterizes multiple fixed points and transitions between them in response to stimuli with diverse time- and amplitude-dependencies. The interplay between the fast dynamics of firing rate and synaptic responses and the slower timescale of synaptic depression makes the neural activity sensitive to the amplitude and duration of square-pulse stimuli in a nontrivial, history-dependent manner. Weak cross-couplings further deform the basins of attraction for different fixed points into intricate shapes. We find that while short-term synaptic depression can reduce the total number of stable fixed points in a network, it tends to strongly increase the number of fixed points visited upon repetitions of fixed stimuli. Our analysis provides a natural explanation for the system's rich responses to stimuli of different durations and amplitudes while demonstrating the encoding capability of bistable neural populations for dynamical features of incoming stimuli. [ABSTRACT FROM AUTHOR]

The article comments on robosports. According to the author, robot technology was that good that most sports fans count not tell the difference. The robots could even act like humans in the pre- and post-match interviews. On the downside, the author believes that the roboplayers are not really smart.

Thailand has been the world's largest exporter of cultured shrimp since 1991. Despite problems with poor environmental conditions and disease outbreaks that led to the failure and abandonment of numerous farms along the coast, Thai shrimp production has remained high. A primary factor has been the establishment of low salinity shrimp farming for black tiger shrimp (Penaeus monodon) in areas much further inlandfrom the coast than once thought feasible. The rapid development of low salinity culture in freshwater areas that are predominantly used for paddy rice cultivation, however, now represents a major land and water management challenge. The debate over the potential environmental impacts of inland shrimp farming revolves around three key questions: i) the ability of so-called 'closed' production systems to minimize environmental impacts, ii) the capacity of the Thai government to enforce environmental protection regulations, and iii) the potential emergence of cumulative environmental impacts. This paper concludes that a ban on inland shrimp farming is a prudent measure, needed to protect soil and water quality in freshwater areas. [ABSTRACT FROM AUTHOR]